Differential upregulation of chemokine receptors on CD56 + NK cells and their transmigration to the site of infection in tuberculous pleurisy

Chemokines and their receptors orchestrate leukocyte recruitment and confer immunity during Mycobacterium tuberculosis infection. The immunoregulatory and cytotoxic activities of natural killer (NK) cells are essential at the site of infection during tuberculous pleurisy. The frequency, subtypes, and expression of phenotype markers and chemokine receptors on NK cells were assessed by flow cytometry in tuberculous (TB) and nontuberculous (NTB) pleural fluid (PF). Chemotaxis was also shown in response to chemokines. A significant decrease in CD56 dim with no change in CD56 bright NK cells was observed, while a significant increase in activation markers and Toll‐like receptors (TLRs) was observed on TB‐PF CD56 bright NK cells. Significantly increased expression of chemokine receptors CCR1, CCR2 and CCR7 on CD56 bright and CCR5 on CD56 dim NK cells was observed in the TB group. Transmigration of TB‐PF NK cells was significantly high in response to IL‐8, IP‐10, MCP‐1 and SLC. Transmigrated TB‐NK cells showed a significant increase in CXCR2, CCR2 and CCR7 expression. The study suggests that CD56 bright NK cells may recognize M. tuberculosis directly using TLRs, HLA‐DR and express CD69 as an early activation marker. In addition, CC chemokines induce activation signals in chemokine receptors mediating differential NK cell migration to the site. Thus, NK cells act as first direct sensors and effectors in mycobacterial infection.